PROJECT SUMMARY/ABSTRACT Limited understanding of factors affecting the course of Osteoarthritis (OA) has hampered development and optimization of strategies that would lessen pain and slow disease progression. While OA is a mechanically- driven disease, important knowledge gaps remain regarding the effects of physical activity, the most common reason for mechanical stimulation of joint structures. OA pain is mainly activity-induced (e.g., stair climbing, walking), but paradoxically, walking regimens can reduce pain. Further, certain degrees of oscillating compressive stress cause trophic changes in cartilage, whereas static or high velocity stress causes catabolic responses. Given the contrasting effects of different types of activities on the joint, it is not surprising that studies of the effects of the amount of physical activity on OA have had conflicting results. Further, it is uncertain what types of activity could be beneficial for pain relief or function improvement without causing harm and accelerating disease progression. The long-term goal of this project is to facilitate decision making for clinicians and patients of a more optimal physical activity regimen for pain relief, maintaining functional performance, and decelerating structural damage in osteoarthritis. The central hypothesis of this proposal is that physical activity's influence on osteoarthritis outcomes differs depending on individual characteristics such as the stage of disease and that different types of activity have different effects on OA outcomes. Further, we hypothesize that the optimal activity regimen may evolve as the patient characteristics change. Therefore, a person-specific physical activity regimen that is adjustable and consistent with the patient's current characteristics is needed. We propose to take advantage of the Osteoarthritis Initiative (OAI) and Multicenter Osteoarthritis Study (MOST) cohorts, two large-scale longitudinal studies on OA with data on physical activity, measured objectively by accelerometer, in addition to extensive clinical, imaging, and medication history data. Our aims are: 1) to characterize the time-varying association of physical activity types with knee OA structural progression, 2) to examine a person-specific and dynamic physical activity regimen for pain reduction in persons with knee OA, and 3) to examine a person-specific and dynamic physical activity regimen for performance-based physical function in persons with knee OA. The contribution of this work is significant because a better understanding of how physical activity types and intensity may improve or worsen the outcomes of OA is urgently needed. Our novel analytic approach is a departure from the traditional approaches of physical activity recommendation based on average effect in the population. Unlike population-oriented approaches that were indifferent to an individual's unique characteristics, our person-specific approach will allow us to adjust the physical activity regimen as the disease evolves. Our work will provide new evidence about diverse types of physical activity and could inform better OA management.